非肝硬化基础上慢加急性肝衰竭恢复期患者发生肝硬化的危险因素分析

李珊珊; 徐曼曼; 段钟平; 陈煜

doi:10.3969/j.issn.1001-5256.2021.12.019

非肝硬化基础上慢加急性肝衰竭恢复期患者发生肝硬化的危险因素分析

DOI: 10.3969/j.issn.1001-5256.2021.12.019

首都医科大学附属北京佑安医院肝病中心四科，肝衰竭与人工肝治疗研究北京市重点实验室，北京 100069

基金项目:

中国肝炎防治基金会-天晴肝病研究基金资助课题 (TQGB20210013);

国家重点研发计划资助 (2017YFA0103000)

详细信息

通信作者:
陈煜，chybeyond1071@ccmu.edu.cn

李珊珊和徐曼曼对本文贡献相同，为共同第一作者

中图分类号: R575.2
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出版历程
- 收稿日期: 2021-04-25
- 录用日期: 2021-05-21
- 出版日期: 2021-12-20

Risk factors for liver cirrhosis in acute-on-chronic liver failure patients without liver cirrhosis in the convalescence stage

Fourth Liver Disease Center, Beijing YouAn Hospital, Capital Medical University; Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing 100069, China

Research funding:

Chinese Foundation for Hepatitis Prevention and Control-TianQing Liver Disease Research Fund Subject (TQGB20210013);

National Key R&D Program of China (2017YFA0103000)

摘要

摘要: 目的探讨影响非肝硬化基础上慢加急性肝衰竭(ACLF)恢复期患者发生肝细胞坏死后肝硬化的危险因素。方法回顾性收集2015年1月—2019年6月首都医科大学附属北京佑安医院收治的ACLF患者临床资料，纳入生存期大于48周和临床资料齐全的非肝硬化基础上ACLF患者57例，根据患者随访48周时是否有肝硬化表现，分为非肝硬化组和肝硬化组，比较两组间的临床指标、无创肝纤维化评分及预后评分，筛选能够独立影响患者进展为肝硬化的因素。正态分布的计量资料两组间比较采用t检验；非正态分布的计量资料两组间比较采用Mann-Whitney U检验；计数资料两组间比较采用χ²检验或Fisher精确检验。采用logistic单因素及多因素分析48周内进展为肝硬化的危险因素，并通过经受试者工作特征曲线(ROC曲线)评估独立危险因素的预测效能。结果 57例患者中有9例(15.8%)患者在随访4周内发生肝硬化，但随访48周肝硬化消失；在随访48周时，26例(45.6%)患者发生肝硬化，将患者分为非肝硬化组(n=31)和肝硬化组(n=26)。肝硬化组的ChE显著低于非肝硬化组[(2844.32±961.05)U/L vs (4137.59±1604.83)U/L，t=3.177, P=0.003]，PLT显著低于非肝硬化组[(100.04±57.28)×10⁹/L vs (138.84±56.46)×10⁹/L，t=2.564, P=0.013]，而肝纤维化评分(FIB-4)显著高于非肝硬化组[7.81 (3.92~11.36) vs 4.45 (2.14~7.80)，Z=258.0，P=0.030]，差异均有统计学意义。将上述指标纳入logistic单因素及多因素回归分析，结果显示低水平的ChE[OR(95%CI)：1.001(1.000~1.002)，P=0.010]和PLT[OR(95%CI)：1.015(1.002~1.028)，P=0.027]是非肝硬化基础上ACLF恢复期患者肝硬化发生的独立危险因素，经ROC曲线分析显示ChE、PLT联合预测非肝硬化基础上ACLF恢复期患者发生肝硬化的价值更高。结论低水平的ChE和PLT是影响非肝硬化基础上ACLF恢复期患者发生肝硬化的独立危险因素，ChE和PLT联合预测更有优势。
- 慢加急性肝功能衰竭 /
- 肝硬化 /
- 危险因素
Abstract: Objective To investigate the risk factors for liver cirrhosis after hepatocyte necrosis in acute-on-chronic liver failure (ACLF) patients without liver cirrhosis in the convalescence stage. Methods A retrospective analysis was performed for the clinical data of ACLF patients who were treated in Beijing YouAn Hospital, Capital Medical University, from January 2015 to June 2019. A total of 57 ACLF patients without liver cirrhosis who had a survival time of > 48 weeks and complete clinical data were enrolled, and according to the presence or absence of liver cirrhosis at week 48 of follow-up, they were divided into non-cirrhosis group and cirrhosis group. The two groups were compared in terms of clinical indices, noninvasive liver fibrosis scores, and prognostic scores to screen out independent influencing factors for progression to liver cirrhosis. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Univariate and multivariate logistic analyses were used to investigate the risk factors for progression to liver cirrhosis within 48 weeks, and the receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency of independent risk factors. Results Among the 57 patients, 9(15.8%) developed liver cirrhosis within 4 weeks of follow-up and showed disappearance of liver cirrhosis at week 48 of follow-up; at week 48 of follow-up, 26 patients (45.6%) developed liver cirrhosis, and the patients were divided into non-cirrhosis group with 31 patients and cirrhosis group with 26 patients. Compared with the non-cirrhosis group, the cirrhosis group had significantly lower levels of cholinesterase (ChE) (2844.32±961.05 U/L vs 4137.59±1604.83 U/L, t=3.177, P=0.003) and platelet count (PLT) [(100.04±57.28)×10⁹/L vs (138.84±56.46)×10⁹/L, t=2.564, P=0.013] and a significantly higher fibrosis-4 score [7.81 (3.92-11.36) vs 4.45 (2.14-7.80), Z=258.0, P=0.030]. The above indices were included in the univariate and multivariate logistic analyses, and the results showed that low levels of ChE (odds ratio [OR]=1.001, 95% confidence interval [CI]: 1.000-1.002, P=0.010) and PLT(OR=1.015, 95%CI: 1.002-1.028, P=0.027) were independent risk factors for liver cirrhosis in ACLF patients without liver cirrhosis in the convalescence stage. The ROC curve analysis showed that the combination of ChE and PLT had a greater value in predicting the onset of liver cirrhosis in ACLF patients without liver cirrhosis in the convalescence stage. Conclusion Low levels of ChE and PLT are independent risk factors for liver cirrhosis in ACLF patients without liver cirrhosis in the convalescence stage, and the combination of ChE and PLT has certain advantages.
- Acute-On-Chronic Liver Failure /
- Liver Cirrhosis /
- Risk Factors

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图 1 回顾性动态观察57例非肝硬化基础上ACLF恢复期患者发生肝硬化情况

下载: 全尺寸图片幻灯片

图 2 预测非肝硬化基础上ACLF恢复期患者48周发生肝硬化的ROC曲线

下载: 全尺寸图片幻灯片

表 1 两组一般资料、实验室指标及相关评分比较

项目	非肝硬化组(n=31)	肝硬化组(n=26)	统计值	P值
男[例(%)]	27(87.1)	22(84.6)		1.000
年龄(岁)	39.61±10.65	43.50±10.60	t=-1.376	0.175
并发症[例(%)]
自发性腹膜炎	29(93.5)	23(88.5)		0.651
腹水	17(54.8)	19(73.1)	χ²=1.314	0.252
肝性脑病	5(16.1)	1(3.8)		0.205
急性肾损伤	3(9.7)	2(7.7)		1.000
上消化道出血	1(3.2)	0		1.000
ALT(U/L)	388.05(140.70~1330.53)	189.60(81.72~507.97)	Z=497.0	0.080
AST(U/L)	250.45(118.35~592.58)	197.40(98.92~406.53)	Z=450.5	0.324
ALP(U/L)	141.00(106.80~164.20)	138.30(120.00~160.70)	Z=197.5	0.968
GGT(U/L)	123.90(80.10~152.50)	79.30(56.00~146.70)	Z=306.0	0.207
Alb(g/L)	31.71±4.73	30.58±4.38	t=0.921	0.361
TBil(μmol/L)	288.74±137.39	319.45±132.47	t=-0.857	0.395
ChE(U/L)	4137.59±1604.83	2844.32±961.05	t=3.177	0.003
INR	2.21 (1.90~2.84)	2.12 (1.73~2.45)	Z=474.0	0.259
Cr(μmol/L)	56.10(47.80~66.50)	63.50(52.25~71.75)	Z=344.5	0.353
Na(mmol/L)	136.95±4.17	136.15±3.27	t=0.818	0.417
AFP(ng/ml)	86.42(32.79~185.45)	88.67(17.68~177.42)	Z=353.0	0.435
Hb(g/L)	133.00±19.50	123.50±20.85	t=1.752	0.086
WBC(×10⁹/L)	7.20(5.35~8.86)	6.44(4.90~9.30)	Z=446.0	0.496
PLT(×10⁹/L)	138.84±56.46	100.04±57.28	t=2.564	0.013
肝纤维化评分
Sheth指数	0.65(0.49~1.05)	1.07(0.55~1.55)	Z=295.0	0.121
APRI指数	6.35(2.25~10.42)	4.93(2.96~9.04)	Z=365.0	0.690
FIB-4指数	4.45(2.14~7.80)	7.81(3.92~11.36)	Z=258.0	0.030
肝衰竭预后评分
MELD-Na评分	21.33±3.75	20.49±4.42	t=0.754	0.455
MELD评分	18.04(13.48~22.00)	16.67(14.16~22.76)	Z=370.0	0.781

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表 2 预测非肝硬化基础上ACLF恢复期患者48周发生肝硬化的单因素和多因素分析

变量	单因素分析		多因素分析
变量	OR(95%CI)	P值	OR(95%CI)	P值
ChE	1.001(1.000~1.002)	0.011	1.001(1.000~1.002)	0.010
PLT	1.013(1.002~1.024)	0.020	1.015(1.002~1.028)	0.027
FIB-4指数	0.933(0.847~1.027)	0.156

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